9-4572480-T-C

Variant names:

• chr9-4572480-T-C
• rs3780412
• NM_004170.6:c.767+92T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004170.6(SLC1A1):​c.767+92T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 1,107,596 control chromosomes in the GnomAD database, including 110,868 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (17610 hom., cov: 33)
  • Exomes 𝑓: 0.43 (93258 hom.)
• Consequence: SLC1A1 NM_004170.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0280
• Publications: 23 publications found

Genes affected

SLC1A1 (HGNC:10939): (solute carrier family 1 member 1) This gene encodes a member of the high-affinity glutamate transporters that play an essential role in transporting glutamate across plasma membranes. In brain, these transporters are crucial in terminating the postsynaptic action of the neurotransmitter glutamate, and in maintaining extracellular glutamate concentrations below neurotoxic levels. This transporter also transports aspartate, and mutations in this gene are thought to cause dicarboxylicamino aciduria, also known as glutamate-aspartate transport defect. [provided by RefSeq, Mar 2010]

SPATA6L (HGNC:25472): (spermatogenesis associated 6 like) Predicted to enable myosin light chain binding activity. Predicted to be involved in spermatogenesis. Predicted to be located in sperm connecting piece. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 9-4572480-T-C is Benign according to our data. Variant chr9-4572480-T-C is described in ClinVar as Benign. ClinVar VariationId is 1266422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A1	NM_004170.6	c.767+92T>C		intron_variant	Intron 7 of 11	ENST00000262352.8	NP_004161.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A1	ENST00000262352.8	c.767+92T>C		intron_variant	Intron 7 of 11	1	NM_004170.6	ENSP00000262352.3
SLC1A1	ENST00000422398.1	c.53+92T>C		intron_variant	Intron 1 of 4	4		ENSP00000414620.1
SPATA6L	ENST00000485616.5	n.*782-18092A>G		intron_variant	Intron 12 of 12	2		ENSP00000420003.1

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71746 AN: 151974 Hom.: 17594 Cov.: 33

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.491

GnomAD4 exome AF: 0.434 AC: 414621 AN: 955502 Hom.: 93258 AF XY: 0.437 AC XY: 217013 AN XY: 496588

African (AFR) AF: 0.595 AC: 14095 AN: 23688

American (AMR) AF: 0.445 AC: 19471 AN: 43756

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 12840 AN: 22948

East Asian (EAS) AF: 0.272 AC: 10158 AN: 37286

South Asian (SAS) AF: 0.479 AC: 35991 AN: 75192

European-Finnish (FIN) AF: 0.334 AC: 17263 AN: 51742

Middle Eastern (MID) AF: 0.567 AC: 2701 AN: 4760

European-Non Finnish (NFE) AF: 0.432 AC: 282095 AN: 652360

Other (OTH) AF: 0.457 AC: 20007 AN: 43770

GnomAD4 genome AF: 0.472 AC: 71809 AN: 152094 Hom.: 17610 Cov.: 33 AF XY: 0.468 AC XY: 34768 AN XY: 74364

African (AFR) AF: 0.590 AC: 24448 AN: 41472

American (AMR) AF: 0.465 AC: 7111 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 1930 AN: 3468

East Asian (EAS) AF: 0.269 AC: 1392 AN: 5178

South Asian (SAS) AF: 0.477 AC: 2299 AN: 4824

European-Finnish (FIN) AF: 0.339 AC: 3579 AN: 10564

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29469 AN: 68002

Other (OTH) AF: 0.492 AC: 1039 AN: 2112

Alfa AF: 0.451 Hom.: 49579

Bravo AF: 0.487

Asia WGS AF: 0.401 AC: 1392 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 20, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.69
DANN	Benign	0.47
PhyloP100		0.028
PromoterAI		0.012	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3780412; hg19: chr9-4572480; COSMIC: COSV52059352;